Ixabepilone and Sunitinib Malate in Treating Patients With Progressive Advanced Solid Tumors
RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of ixabepilone when given together with sunitinib malate in treating patients with progressive advanced solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
Other: Angiogenesis Biomarker Analysis
Other: Pharmacokinetic Design
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of Weekly and Every Three Weeks Ixabepilone and Sunitinib in Solid Tumor Patients|
- Safety and toxicity profile as assessed by NCI CTCAE version 3.0 [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: Yes ]
- Recommended Phase II dose of Ixabepilone when administered with Sunitinib [ Time Frame: Schedule A (12 - 18 months); Schedule B (6 -12 months after Schedule A) ] [ Designated as safety issue: Yes ]
- Pharmacokinetic profiles of Ixabepilone and Sunitinib malate and correlation with activity and/or toxicity [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: No ]
- Efficacy data (complete response, partial response, or stable disease) of these treatment combinations [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: No ]
- Correlation of changes in angiogenesis biomarkers with clinical (safety and efficacy) and pharmacokinetic parameters [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: No ]
- Estimation of optimal biological dose [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: No ]
|Study Start Date:||November 2008|
|Estimated Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
|Experimental: Ixabepilone and Sunitinib||
Administered intravenously. Dosage assigned by Phase I center as determined by dose-escalation schedule:
Other Names:Drug: Sunitinib
For both Schedules A and B, daily, orally, starting on Day 8 of Cycle 1
Other Names:Other: Angiogenesis Biomarker Analysis
Other: Pharmacokinetic Design
The following studies will be performed in the blood of study subjects:
Pharmacokinetic sampling taken according to dose schedule (Schedule A or Schedule B) as per protocol.
- To determine the safety and toxicity profile of ixabepilone in combination with sunitinib malate in patients with progressive, advanced non-hematologic malignancies.
- To determine the recommended phase II dose of ixabepilone given weekly versus once every three weeks in combination with a fixed dose of sunitinib malate in these patients.
- To evaluate the pharmacokinetic profiles of the combination of ixabepilone and sunitinib malate and correlate them with activity and/or toxicity.
- To obtain preliminary efficacy data (complete response, partial response, or stable disease) of these treatment combinations.
- To correlate changes in angiogenesis biomarkers with clinical (safety and efficacy) and pharmacokinetic parameters in patients treated with these drug combinations.
- To estimate the optimal biological dose.
OUTLINE: This is a dose escalation study of ixabepilone. Patients are assigned to 1 of 2 treatment groups.
- Schedule A: Patients receive ixabepilone IV on days 1, 8, and 15. Beginning on day 8 of course 1, patients also receive oral sunitinib malate once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Schedule B: Patients receive ixabepilone IV on day 1. Beginning on day 8 of course 1, patients also receive oral sunitinib malate once daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for biomarker and pharmacokinetic studies by flow cytometry.
After completion of study therapy, patients are followed at 30 days and every 3 months for 1 year.
|United States, Florida|
|University of Miami Sylvester Comprehensive Cancer Center|
|Miami, Florida, United States, 33136|
|Study Chair:||Jaime R. Merchan, MD||University of Miami Sylvester Comprehensive Cancer Center|